What should be done if hepatitis is suspected due to haloperidol (antipsychotic medication) use?

Management of Haloperidol-Induced Hepatitis

When hepatitis is suspected due to haloperidol use, the medication should be immediately discontinued and alternative antipsychotic treatment with a lower hepatotoxicity risk should be considered. 1

Assessment and Diagnosis

• Haloperidol-induced hepatitis is considered when ALT levels are ≥3 times the upper limit of normal with hepatitis symptoms, or ≥5 times the upper limit of normal without symptoms 2
• Monitor for clinical symptoms of hepatotoxicity including:
  • Jaundice
  • Fatigue
  • Abdominal pain
  • Nausea/vomiting
  • Dark urine
  • Pruritus 2
• Obtain comprehensive liver function tests including ALT, AST, alkaline phosphatase, bilirubin, and coagulation studies 2
• Consider liver biopsy in cases of grade 2 hepatitis or higher to confirm diagnosis and rule out other causes 3

Management Algorithm

Grade 1 Hepatitis (AST/ALT 1-3× ULN or total bilirubin 1-1.5× ULN):

• Discontinue haloperidol immediately 1
• Monitor liver function tests once or twice weekly 3
• Consider consultation with gastroenterology/hepatology 3

Grade 2 Hepatitis (AST/ALT >3-5× ULN or total bilirubin >1.5-3× ULN):

• Discontinue haloperidol immediately 1
• Consult with gastroenterology or hepatology 3
• Discontinue all other potential hepatotoxins if medically feasible 3
• Consider prednisone 0.5-1.0 mg/kg/day if patient has clinical symptoms of liver toxicity 3
• Monitor liver function tests closely 3

Grade 3 Hepatitis (AST/ALT >5-20× ULN or total bilirubin >3-10× ULN):

• Discontinue haloperidol immediately 1
• Urgent consultation with gastroenterology/hepatology 3
• Consider hospitalization for urgent management 3
• Initiate glucocorticoids at 1-2 mg/kg methylprednisolone or equivalent with a planned 4-6 week taper 3
• Consider liver biopsy to confirm diagnosis 3

Grade 4 Hepatitis (AST/ALT >20× ULN or total bilirubin >10× ULN or hepatic decompensation):

• Hospitalize patient, preferably at a center with expertise in liver failure 3
• Discontinue haloperidol permanently 3
• Start methylprednisolone 2 mg/kg/day or equivalent with a planned 4-6 week taper 3
• Consider second-line immunosuppression (azathioprine, mycophenolate mofetil, or tacrolimus) if no improvement within 3 days 3

Alternative Antipsychotic Selection

• When switching from haloperidol, consider antipsychotics with lower hepatotoxicity risk 1:
  • Paliperidone, aripiprazole, lurasidone, and loxapine have the lowest risk with no reports of liver failure 1
  • Avoid chlorpromazine, clozapine, and olanzapine which pose the greatest risk of hepatotoxicity 1
  • Quetiapine and risperidone pose moderate risk 1

Monitoring After Discontinuation

• Continue monitoring liver function tests until normalization 2
• Be aware of potential cross-toxicity with other antipsychotics 4
• Maintain documentation of haloperidol-induced hepatitis in patient's medical record to avoid re-exposure 2

Important Considerations and Pitfalls

• Drug-induced hepatitis is often idiosyncratic and unpredictable, generally unrelated to drug dosage 4
• The interval between treatment initiation and onset of liver injury is generally between several days and 6 months 4
• Patients with pre-existing liver disease or excessive alcohol consumption are at higher risk for drug-induced hepatotoxicity 2
• Cross-toxicity between antipsychotics can occur, so careful selection of alternative medication is essential 4
• Avoid assuming that mild transaminase elevations will resolve without intervention - prompt discontinuation of the offending drug is essential 2